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VUMC research team receives $1 million grant from AHA to study impact of long-COVID on heart

Apr. 14, 2022, 3:30 PM

by Bill Snyder

(L-R) Italo Biaggioni, MD, Cyndya Shibao, MD, MSCI, Meena Madhur, MD, PhD, and Luis Okamoto, PhD, are studying the long-term effects of COVID-19 on the heart. (Photo by Donn Jones)

A research team led by Cyndya Shibao, MD, MSCI, associate professor of Medicine at Vanderbilt University Medical Center (VUMC), has received a major grant from the American Heart Association to study long-term effects of COVID-19 on the heart and cardiovascular system. 

The three-year, $1million grant was one of 11 awards announced April 14 by the AHA. 

An estimated one in 10 people who recover from COVID-19 will develop chronic, debilitating symptoms including fatigue, chest pain, and reduced exercise tolerance with an abnormally rapid heart rate (tachycardia) that persist for weeks beyond the initial viral infection. 

Some of these post-acute or “long-COVID” patients develop symptoms suggestive of postural tachycardia syndrome (POTS), a disorder that primarily affects women and which is characterized by lightheadedness, extreme fatigue, and chronic tachycardia upon standing (orthostatic intolerance). 

“Our goal,” said Shibao, “is to discover new treatment pathways for this disabling disease.” 

While the cause is unknown, elevated levels of pro-inflammatory proteins called cytokines have been detected in the blood of long-COVID patients with symptoms of POTS, suggesting that unresolved inflammation may play a role in this novel syndrome. 

In a preliminary study, the VUMC researchers found that these patients exhibited reduced activity of the parasympathetic nervous system, which normally modulates inflammation by acting as an anti-inflammatory neural circuit. 

To determine if increased inflammation is associated with reduced parasympathetic activity, the researchers will compare parasympathetic activity and immune activation in long-COVID patients with POTS-like symptoms to controls who have a history of COVID-19 but who have not experienced long-term consequences (sequelae). 

Meena Madhur, MD, PhD, and colleagues will perform immunophenotyping of patients with post-acute COVID tachycardia and controls using a variety of methods including CITE-Seq, a single-cell method that provides surface proteomic and transcriptomic data. 

Madhur is associate professor of Medicine and Molecular Physiology & Biophysics, and associate director of the Vanderbilt Institute for Infection, Immunology and Inflammation. 

The researchers also will test whether restoring parasympathetic function through transcutaneous vagus nerve stimulationreduces inflammation and improves orthostatic intolerance and other symptoms. Electrically stimulating the vagus nerve across the skin reduces cytokine production and has been shown in animal models to reduce the severity of inflammatory syndromes. 

Luis Okamoto, MD, research assistant of Medicine, will collaborate in the characterization of the clinical and autonomic profiles of patients with post-acute COVID POTS, and in studies of chronic transcutaneous vagus nerve stimulation. 

Italo Biaggioni, MD, the David Robertson, MD, Professor of Autonomic Disorders and professor of Medicine and Pharmacology, also will participate in the study. Biaggioni was recognized last year by the American Heart Association as a Distinguished Scientist for his contributions to cardiovascular research.

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